Lüscher-Firzlaff Juliane M, Lilischkis Richard, Lüscher Bernhard
Abteilung Biochemie und Molekularbiologie, Institut für Biochemie, Universitätsklinikum der RWTH, Pauwelsstrasse 30, 52057 Aachen, Germany.
FEBS Lett. 2006 Mar 20;580(7):1716-22. doi: 10.1016/j.febslet.2006.02.021. Epub 2006 Feb 20.
The FOXM1 forkhead proteins, originally identified as M-phase phosphoproteins, are proliferation-associated transcriptional regulators involved in cell cycle progression, genetic stability and tumorigenesis. Here we demonstrate that Cyclin-dependent kinases regulate the transcriptional activity of FOXM1c. This is independent of an N-terminal negative regulatory domain and of the forkhead DNA binding domain. Instead we mapped the responsive sites in the transactivation domain. A combination of three phosphorylation sites mediates the Cyclin E and Cyclin A/CDK2 effects. Our findings provide evidence for a novel Cyclin E/CDK2 substrate that functions in cell cycle control.
FOXM1叉头蛋白最初被鉴定为M期磷酸化蛋白，是与增殖相关的转录调节因子，参与细胞周期进程、遗传稳定性和肿瘤发生。在此我们证明，细胞周期蛋白依赖性激酶调节FOXM1c的转录活性。这独立于N端负调节域和叉头DNA结合域。相反，我们在反式激活域中定位了反应位点。三个磷酸化位点的组合介导了细胞周期蛋白E和细胞周期蛋白A/细胞周期蛋白依赖性激酶2的作用。我们的研究结果为一种在细胞周期控制中起作用的新型细胞周期蛋白E/细胞周期蛋白依赖性激酶2底物提供了证据。
